Structural basis of interaction between dimeric cyclophilin 1 and Myb1 transcription factor in Trichomonas vaginalis.

Cyclophilin 1 (TvCyP1), a cyclophilin type peptidyl-prolyl isomerase present in the human parasite Trichomonas vaginalis, interacts with Myb1 and assists in its nuclear translocation. Myb1 regulates the expression of ap65-1 gene that encodes for a disease causing cytoadherence enzyme. Here, we determined the crystal structures of TvCyP1 and its complex with the minimum TvCyP1-binding sequence of Myb1 (Myb1), where TvCyP1 formed a homodimer, unlike other single domain cyclophilins. In the complex structure, one Myb1 peptide was bound to each TvCyP1 protomer, with G106-P107 and Y105 fitting well into the active site and auxiliary S2 pocket, respectively. NMR data further showed that TvCyP1 can catalyze the cis/trans isomerization of P107 in Myb1. Interestingly, in the well-folded Myb1 protein (Myb1), the minimum binding sequence adopted a different conformation from that of unstructured Myb1 peptide, that could make P107 binding to the active site of TvCyP1 difficult. However, NMR studies showed that similar to Myb1 peptide, Myb1 also interacted with the active site of TvCyP1 and the dynamics of the Myb1 residues near P107 was reduced upon interaction. Together, the structure of TvCyP1 and detailed structural insights on TvCyP1-Myb1 interaction provided here could pave the way for newer drugs to treat drug-resistant strains.